De Cock Pieter A J G, Desmet Sarah, De Jaeger Annick, Biarent Dominique, Dhont Evelyn, Herck Ingrid, Vens Daphné, Colman Sofie, Stove Veronique, Commeyne Sabrina, Vande Walle Johan, De Paepe Peter
Department of Pharmacy, Ghent University Hospital, Ghent, Belgium.
Heymans Institute of Pharmacology, Ghent University, Ghent, Belgium.
J Antimicrob Chemother. 2017 Mar 1;72(3):801-804. doi: 10.1093/jac/dkw495.
The objectives of this observational study were to investigate plasma protein binding and to evaluate target attainment rates of vancomycin therapy in critically ill children.
Paediatric ICU patients, in whom intravenous intermittent dosing (ID) or continuous dosing (CD) with vancomycin was indicated, were included. Covariates on unbound vancomycin fraction and concentration were tested using a linear mixed model analysis and attainment of currently used pharmacokinetic/pharmacodynamic (PK/PD) targets was evaluated. Clinicaltrials.gov: NCT02456974.
One hundred and eighty-eight plasma samples were collected from 32 patients. The unbound vancomycin fraction (median = 71.1%; IQR = 65.4%-79.7%) was highly variable within and between patients and significantly correlated with total protein and albumin concentration, which were both decreased in our population. Total trough concentration (ID) and total concentration (CD) were within the aimed target concentrations in 8% of patients. The targets of AUC/MIC ≥400 and f AUC/MIC ≥200 were achieved in 54% and 83% of patients, respectively. Unbound vancomycin concentrations were adequately predicted using the following equation: unbound vancomycin concentration (mg/L) = 5.38 + [0.71 × total vancomycin concentration (mg/L)] - [0.085 × total protein concentration (g/L)]. This final model was externally validated using 51 samples from another six patients.
The protein binding of vancomycin in our paediatric population was lower than reported in non-critically ill adults and exhibited large variability. Higher target attainment rates were achieved when using PK/PD indices based on unbound concentrations, when compared with total concentrations. These results highlight the need for protein binding assessment in future vancomycin PK/PD research.
本观察性研究的目的是调查血浆蛋白结合情况，并评估重症儿童万古霉素治疗的目标达成率。
纳入了需要静脉间歇给药（ID）或持续给药（CD）万古霉素的儿科重症监护病房患者。使用线性混合模型分析对未结合万古霉素分数和浓度的协变量进行测试，并评估当前使用的药代动力学/药效学（PK/PD）目标的达成情况。Clinicaltrials.gov：NCT02456974。
从32例患者中采集了188份血浆样本。未结合万古霉素分数（中位数=71.1%；四分位数间距=65.4%-79.7%）在患者内部和患者之间高度可变，且与总蛋白和白蛋白浓度显著相关，而这两者在我们的研究人群中均降低。8%的患者的总谷浓度（ID）和总浓度（CD）在目标浓度范围内。分别有54%和83%的患者达到了AUC/MIC≥400和f AUC/MIC≥200的目标。使用以下公式可充分预测未结合万古霉素浓度：未结合万古霉素浓度（mg/L）=5.38+[0.71×总万古霉素浓度（mg/L）]-[0.085×总蛋白浓度（g/L）]。使用来自另外6例患者的51份样本对该最终模型进行了外部验证。
我们儿科人群中万古霉素的蛋白结合低于非重症成人报道的水平，且表现出很大的变异性。与总浓度相比，使用基于未结合浓度的PK/PD指标时目标达成率更高。这些结果凸显了在未来万古霉素PK/PD研究中进行蛋白结合评估的必要性。
